View source for Purine nucleoside phosphorylase

{{Inline citations|date=September 2017}}{{Distinguish|polynucleotide phosphorylase}}
{{enzyme
| Name = purine-nucleoside phosphorylase
| EC_number = 2.4.2.1
| CAS_number = 9030-21-1
| IUBMB_EC_number = 2/4/2/1
| GO_code = 0004731
| image = 1rct.png
| width = 
| caption = purine-nucleoside phosphorylase. [[Protein Data Bank|PDB]] 1rct.<ref>{{cite journal | vauthors = Canduri F, dos Santos DM, Silva RG, Mendes MA, Basso LA, Palma MS, de Azevedo WF, Santos DS | title = Structures of human purine nucleoside phosphorylase complexed with inosine and ddI | journal = Biochemical and Biophysical Research Communications | volume = 313 | issue = 4 | pages = 907–14 | date = Jan 2004 | pmid = 14706628 | doi = 10.1016/j.bbrc.2003.11.179 }}</ref>
}}
{{Infobox_gene}}
'''Purine nucleoside phosphorylase''' ('''PNP''') also known as '''PNPase''' and '''inosine phosphorylase''' is an [[enzyme]] that in humans is encoded by the ''NP'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NP nucleoside phosphorylase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4860| accessdate = }}</ref>

In [[enzymology]], a purine-nucleoside phosphorylase ({{EC number|2.4.2.1}}) is an [[enzyme]] that [[catalysis|catalyzes]] the [[chemical reaction]]

:purine nucleoside + phosphate <math>\rightleftharpoons</math> purine + alpha-D-ribose 1-phosphate

Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are [[purine nucleoside]] and [[phosphate]], whereas its two [[product (chemistry)|products]] are [[purine]] and [[alpha-D-ribose 1-phosphate]].

== Nomenclature ==

This enzyme belongs to the family of [[glycosyltransferase]]s, specifically the pentosyltransferases.  The [[List of enzymes|systematic name]] of this enzyme class is '''purine-nucleoside:phosphate ribosyltransferase'''.

Other names in common use include:
{{div col|colwidth=20em}}
* inosine phosphorylase,
* PNPase,
* PUNPI,
* PUNPII,
* inosine-guanosine phosphorylase,
* nucleotide phosphatase,
* purine deoxynucleoside phosphorylase,
* purine deoxyribonucleoside phosphorylase,
* purine nucleoside phosphorylase,
* and purine ribonucleoside phosphorylase.  
{{Div col end}}

This enzyme participates in 3 [[metabolism|metabolic pathways]]: [[purine metabolism]], [[pyrimidine metabolism]], and [[nicotinate and nicotinamide metabolism]].

== Function ==
Purine nucleoside phosphorylase is an enzyme involved in [[Purine#Metabolism|purine metabolism]]. PNP metabolizes [[inosine]] into [[hypoxanthine]] and [[guanosine]] into [[guanine]], in each case creating [[ribose phosphate]]. Note: [[adenosine]] is first metabolized to  [[inosine]] via the enzyme adenosine deaminase.<ref>Kaplan USMLE Biochemistry Review</ref>

Nucleoside phosphorylase is an enzyme which cleaves a nucleoside by [[Phosphorylation|phosphorylating]] the ribose to produce a [[nucleobase]] and ribose 1 phosphate. It is one enzyme of the [[nucleotide salvage]] pathways. These pathways allow the cell to produce nucleotide monophosphates when the [[de novo synthesis|''de novo'' synthesis]] pathway has been interrupted or is non-existent (as is the case in the brain). Often the de novo pathway is interrupted as a result of [[chemotherapy]] drugs such as [[methotrexate]] or [[aminopterin]].

All salvage pathway enzymes require a high energy [[phosphate]] donor such as [[Adenosine triphosphate|ATP]] or [[PRPP]].

* [[Thymidine]] can be phosphorylated by [[thymidine kinase]] (TK).
* [[Uridine]] can be phosphorylated by [[uridine kinase]] (UK).
* [[Cytidine]] can be phosphorylated by [[cytidine kinase]] (CK).
* [[Deoxycytidine]] can be phosphorylated by [[deoxycytidine kinase]] (DCK).

[[Adenosine]] uses the enzyme [[adenosine kinase]], which is a very important enzyme in the cell. Attempts are being made to develop an inhibitor for the enzyme for use in [[cancer]] chemotherapy.

== Enzyme regulation ==

This protein may use the [[morpheein]] model of [[allosteric regulation]].<ref name=pmid22182754>{{cite journal | vauthors = Selwood T, Jaffe EK | title = Dynamic dissociating homo-oligomers and the control of protein function | journal = Archives of Biochemistry and Biophysics | volume = 519 | issue = 2 | pages = 131–43 | date = Mar 2012 | pmid = 22182754 | pmc = 3298769 | doi = 10.1016/j.abb.2011.11.020 }}</ref>

== Clinical significance ==

PNPase, together with adenosine deaminase (ADA), serves a key role in purine catabolism, referred to as the salvage pathway. Mutations in ADA lead to an accumulation of (d)ATP, which inhibits [[ribonucleotide reductase]], leading to a deficiency in (d)CTPs and (d)TTPs, which, in turn, induces [[apoptosis]] in T-lymphocytes and B-lymphocytes, leading to [[severe combined immunodeficiency]] (SCID).{{Citation needed|date=November 2010}}

PNP-deficient patients will have an immunodeficiency problem.  It affects only T-cells; B-cells are unaffected by the deficiency.

== See also ==
* [[Purine nucleoside phosphorylase deficiency]]

== References ==
{{reflist}}

== Further reading ==
{{Refbegin| 2}}
* {{cite journal | vauthors = Markert ML | title = Purine nucleoside phosphorylase deficiency | journal = Immunodeficiency Reviews | volume = 3 | issue = 1 | pages = 45–81 | year = 1991 | pmid = 1931007 | doi =  }}
* {{cite journal | vauthors = Borgers M, Verhaegen H, De Brabander M, De Cree J, De Cock W, Thoné F, Geuens G | title = Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL) | journal = Blood | volume = 52 | issue = 5 | pages = 886–95 | date = Nov 1978 | pmid = 100152 | doi =  }}
* {{cite journal | vauthors = Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML | title = Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency | journal = American Journal of Human Genetics | volume = 51 | issue = 4 | pages = 763–72 | date = Oct 1992 | pmid = 1384322 | pmc = 1682776 | doi =  }}
* {{cite journal | vauthors = Andrews LG, Markert ML | title = Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency | journal = The Journal of Biological Chemistry | volume = 267 | issue = 11 | pages = 7834–8 | date = Apr 1992 | pmid = 1560016 | doi =  }}
* {{cite journal | vauthors = Jonsson JJ, Williams SR, McIvor RS | title = Sequence and functional characterization of the human purine nucleoside phosphorylase promoter | journal = Nucleic Acids Research | volume = 19 | issue = 18 | pages = 5015–20 | date = Sep 1991 | pmid = 1923769 | pmc = 328804 | doi = 10.1093/nar/19.18.5015 }}
* {{cite journal | vauthors = Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE | title = Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution | journal = The Journal of Biological Chemistry | volume = 265 | issue = 3 | pages = 1812–20 | date = Jan 1990 | pmid = 2104852 | doi =  }}
* {{cite journal | vauthors = Williams SR, Gekeler V, McIvor RS, Martin DW | title = A human purine nucleoside phosphorylase deficiency caused by a single base change | journal = The Journal of Biological Chemistry | volume = 262 | issue = 5 | pages = 2332–8 | date = Feb 1987 | pmid = 3029074 | doi =  }}
* {{cite journal | vauthors = Williams SR, Goddard JM, Martin DW | title = Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization | journal = Nucleic Acids Research | volume = 12 | issue = 14 | pages = 5779–87 | date = Jul 1984 | pmid = 6087295 | pmc = 320030 | doi = 10.1093/nar/12.14.5779 }}
* {{cite journal | vauthors = Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K | title = Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient | journal = Human Genetics | volume = 98 | issue = 6 | pages = 706–9 | date = Dec 1996 | pmid = 8931706 | doi = 10.1007/s004390050290 }}
* {{cite journal | vauthors = Markert ML, Finkel BD, McLaughlin TM, Watson TJ, Collard HR, McMahon CP, Andrews LG, Barrett MJ, Ward FE | title = Mutations in purine nucleoside phosphorylase deficiency | journal = Human Mutation | volume = 9 | issue = 2 | pages = 118–21 | year = 1997 | pmid = 9067751 | doi = 10.1002/(SICI)1098-1004(1997)9:2<118::AID-HUMU3>3.0.CO;2-5 }}
* {{cite journal | vauthors = Erion MD, Takabayashi K, Smith HB, Kessi J, Wagner S, Hönger S, Shames SL, Ealick SE | title = Purine nucleoside phosphorylase. 1. Structure-function studies | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11725–34 | date = Sep 1997 | pmid = 9305962 | doi = 10.1021/bi961969w }}
* {{cite journal | vauthors = Erion MD, Stoeckler JD, Guida WC, Walter RL, Ealick SE | title = Purine nucleoside phosphorylase. 2. Catalytic mechanism | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11735–48 | date = Sep 1997 | pmid = 9305963 | doi = 10.1021/bi961970v }}
* {{cite journal | vauthors = Stoeckler JD, Poirot AF, Smith RM, Parks RE, Ealick SE, Takabayashi K, Erion MD | title = Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis | journal = Biochemistry | volume = 36 | issue = 39 | pages = 11749–56 | date = Sep 1997 | pmid = 9305964 | doi = 10.1021/bi961971n }}
* {{cite journal | vauthors = Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R | title = Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient | journal = Human Genetics | volume = 103 | issue = 1 | pages = 81–5 | date = Jul 1998 | pmid = 9737781 | doi = 10.1007/s004390050787 }}
* {{cite journal | vauthors = Sheppard TL, Ordoukhanian P, Joyce GF | title = A DNA enzyme with N-glycosylase activity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 7802–7 | date = Jul 2000 | pmid = 10884411 | pmc = 16625 | doi = 10.1073/pnas.97.14.7802 }}
* {{cite journal | vauthors = Dalal I, Grunebaum E, Cohen A, Roifman CM | title = Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient | journal = Clinical Genetics | volume = 59 | issue = 6 | pages = 430–7 | date = Jun 2001 | pmid = 11453975 | doi = 10.1034/j.1399-0004.2001.590608.x }}
* {{cite journal | vauthors = Ivings L, Pennington SR, Jenkins R, Weiss JL, Burgoyne RD | title = Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin | journal = The Biochemical Journal | volume = 363 | issue = Pt 3 | pages = 599–608 | date = May 2002 | pmid = 11964161 | pmc = 1222513 | doi = 10.1042/0264-6021:3630599 }}
* {{cite journal | vauthors = Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM | title = Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA | journal = Nature Genetics | volume = 31 | issue = 3 | pages = 289–94 | date = Jul 2002 | pmid = 12068295 | doi = 10.1038/ng909 }}
* {{cite journal | vauthors = Stoychev G, Kierdaszuk B, Shugar D | title = Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems | journal = European Journal of Biochemistry / FEBS | volume = 269 | issue = 16 | pages = 4048–57 | date = Aug 2002 | pmid = 12180982 | doi = 10.1046/j.1432-1033.2002.03097.x }}
* {{cite journal |vauthors=Agarwal RP, Parks RE | date = 1969 | title = Purine nucleoside phosphorylase from human erythrocytes. IV Crystallization and some properties | journal = J. Biol. Chem.  | volume = 244 | pages = 644&ndash;7  | pmid = 5768862 | issue = 4 }}
* Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 5, Academic Press, New York, 1961, p.&nbsp;237-255.
* {{cite journal |vauthors=HEPPEL LA, HILMOE RJ | date = 1952 | title = [Phosphorolysis and hydrolysis of purine ribosides by enzymes from yeast.] | journal = J. Biol. Chem.  | volume = 198 | pages = 683&ndash;94  | pmid = 12999785 | issue = 2 }}
* {{cite journal | author = Kalckar HM | date = 1947 | title = The enzymatic synthesis of purine ribosides | journal = J. Biol. Chem.  | volume = 167 | pages = 477&ndash;486 | pmid=20285042}}
* {{cite journal |vauthors=Saunders PP, Wilson BA, Saunders GF | date = 1969 | title = Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus | journal = J. Biol. Chem.  | volume = 244 | pages = 3691&ndash;7  | pmid = 4978445 | issue = 13 }}
* {{cite journal |vauthors=Tsuboi KK, Hudson PB| date = 1957 | title = Enzymes of the human erythrocyte. I. Purine nucleoside phosphorylase; isolation procedure | journal = J. Biol. Chem.  | volume = 224 | pages = 879&ndash;887 | pmid=13405917}}

{{Refend}}

== External links ==
*[http://arginine.chem.cornell.edu/Structures/HumanPNP.html Human PNP] at [[Cornell University]]
*[http://arginine.chem.cornell.edu/Structures/ECPNP.html E. Coli PNP] at [[Cornell University]]
*{{MeshName|Purine-Nucleoside+Phosphorylase}}

{{PDB Gallery|geneid=4860}}
{{Nucleotide metabolism}}
{{Glycosyltransferases}}
{{Enzymes}}
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[[Category:EC 2.4.2]]
[[Category:Enzymes of known structure]]